Inhibition of 4-(Methylnitrosamino)-l-(3-pyridyl)-l-butanone-induced DNA Adduct Formation and Tumorigenicity in the Lung of F344 Rats by Dietary Phenethyl Isothiocyanate

Mark A. Morse, Chung Xiou Wang, Gary D. Stonei, Swapna Manda, Philip B. Conran, Shantu Amin, Stephen S. Hecht, Fung Lung Chung

Research output: Contribution to journalArticle

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Abstract

F344 rats fed diets containing phenethyl isothiocyanate (PEITC, 3 μmol/g diet), a cruciferous vegetable component, before and during treatment with the tobacco-specific carcinogen 4-(methylnitrosamino)-l-(3-pyridyl)-1-butanone (NNK), developed about 50% fewer lung tumors than NNK-treated rats fed control diets. NNK-induced liver and nasal cavity tumors in rats were, however, not affected by this dietary treatment. The effects of PEITC diets on the formation of DNA adducts by NNK were also investigated in these target tissues. DNA methylation and pyridyloxobutylation by NNK were both decreased by 50% in lung of rats fed PEITC diets compared to that of rats fed control diets, but the levels of DNA methylation were not affected in liver and nasal mucosa. These results correlated with those from the carcinogenicity bioassay, suggesting that DNA alkylations could be used as indicators for screening inhibitors of NNK tumorigenesis. A slight increase in the number of tumors of the exocrine pancreas was observed in PEITC-fed rats with or without NNK treatments. However, these incidences were not statistically significant when compared to the control groups. The potential toxicity of PEITC at concentrations ranging from 0.75 mmol to 6 μmol/g diet was evaluated in a 13-week study. The only toxicity caused by this treatment was minimal fatty metamorphosis in the liver. Considering the widespread human exposure to NNK through tobacco use, it is of practical importance to demonstrate inhibition of lung tumors induced by this carcinogen. These results provide a basis for studies designed to discover agents of better efficacy for the prevention of NNK-induced tumorigenesis.

Original languageEnglish (US)
Pages (from-to)549-553
Number of pages5
JournalCancer Research
Volume49
Issue number3
StatePublished - Feb 1 1989

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Butanones
DNA Adducts
Inbred F344 Rats
Diet
Lung
DNA Methylation
Carcinogens
Liver
Neoplasms
Carcinogenesis
Exocrine Pancreas
Nasal Mucosa
Nasal Cavity
Alkylation
Tobacco Use
phenethyl isothiocyanate
Biological Assay
Vegetables
Tobacco
Control Groups

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Morse, Mark A. ; Wang, Chung Xiou ; Stonei, Gary D. ; Manda, Swapna ; Conran, Philip B. ; Amin, Shantu ; Hecht, Stephen S. ; Chung, Fung Lung. / Inhibition of 4-(Methylnitrosamino)-l-(3-pyridyl)-l-butanone-induced DNA Adduct Formation and Tumorigenicity in the Lung of F344 Rats by Dietary Phenethyl Isothiocyanate. In: Cancer Research. 1989 ; Vol. 49, No. 3. pp. 549-553.
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title = "Inhibition of 4-(Methylnitrosamino)-l-(3-pyridyl)-l-butanone-induced DNA Adduct Formation and Tumorigenicity in the Lung of F344 Rats by Dietary Phenethyl Isothiocyanate",
abstract = "F344 rats fed diets containing phenethyl isothiocyanate (PEITC, 3 μmol/g diet), a cruciferous vegetable component, before and during treatment with the tobacco-specific carcinogen 4-(methylnitrosamino)-l-(3-pyridyl)-1-butanone (NNK), developed about 50{\%} fewer lung tumors than NNK-treated rats fed control diets. NNK-induced liver and nasal cavity tumors in rats were, however, not affected by this dietary treatment. The effects of PEITC diets on the formation of DNA adducts by NNK were also investigated in these target tissues. DNA methylation and pyridyloxobutylation by NNK were both decreased by 50{\%} in lung of rats fed PEITC diets compared to that of rats fed control diets, but the levels of DNA methylation were not affected in liver and nasal mucosa. These results correlated with those from the carcinogenicity bioassay, suggesting that DNA alkylations could be used as indicators for screening inhibitors of NNK tumorigenesis. A slight increase in the number of tumors of the exocrine pancreas was observed in PEITC-fed rats with or without NNK treatments. However, these incidences were not statistically significant when compared to the control groups. The potential toxicity of PEITC at concentrations ranging from 0.75 mmol to 6 μmol/g diet was evaluated in a 13-week study. The only toxicity caused by this treatment was minimal fatty metamorphosis in the liver. Considering the widespread human exposure to NNK through tobacco use, it is of practical importance to demonstrate inhibition of lung tumors induced by this carcinogen. These results provide a basis for studies designed to discover agents of better efficacy for the prevention of NNK-induced tumorigenesis.",
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Inhibition of 4-(Methylnitrosamino)-l-(3-pyridyl)-l-butanone-induced DNA Adduct Formation and Tumorigenicity in the Lung of F344 Rats by Dietary Phenethyl Isothiocyanate. / Morse, Mark A.; Wang, Chung Xiou; Stonei, Gary D.; Manda, Swapna; Conran, Philip B.; Amin, Shantu; Hecht, Stephen S.; Chung, Fung Lung.

In: Cancer Research, Vol. 49, No. 3, 01.02.1989, p. 549-553.

Research output: Contribution to journalArticle

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T1 - Inhibition of 4-(Methylnitrosamino)-l-(3-pyridyl)-l-butanone-induced DNA Adduct Formation and Tumorigenicity in the Lung of F344 Rats by Dietary Phenethyl Isothiocyanate

AU - Morse, Mark A.

AU - Wang, Chung Xiou

AU - Stonei, Gary D.

AU - Manda, Swapna

AU - Conran, Philip B.

AU - Amin, Shantu

AU - Hecht, Stephen S.

AU - Chung, Fung Lung

PY - 1989/2/1

Y1 - 1989/2/1

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